EP0327259B1 - Verwendung eines Mittels zum Fördern des Tierwachstums - Google Patents

Verwendung eines Mittels zum Fördern des Tierwachstums Download PDF

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Publication number
EP0327259B1
EP0327259B1 EP89300764A EP89300764A EP0327259B1 EP 0327259 B1 EP0327259 B1 EP 0327259B1 EP 89300764 A EP89300764 A EP 89300764A EP 89300764 A EP89300764 A EP 89300764A EP 0327259 B1 EP0327259 B1 EP 0327259B1
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EP
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Prior art keywords
water
methanol
salt
glycopeptide
salts
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Expired - Lifetime
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EP89300764A
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English (en)
French (fr)
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EP0327259A2 (de
EP0327259A3 (en
Inventor
Yoshiyuki Hayashi
Takao Konishi
Koichi Matsumoto
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Shionogi and Co Ltd
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Shionogi and Co Ltd
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Priority to AT89300764T priority Critical patent/ATE88614T1/de
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Publication of EP0327259A3 publication Critical patent/EP0327259A3/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/195—Antibiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K9/00—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof
    • C07K9/006—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure
    • C07K9/008—Peptides having up to 20 amino acids, containing saccharide radicals and having a fully defined sequence; Derivatives thereof the peptide sequence being part of a ring structure directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin

Definitions

  • the invention relates to the use of an agent for animal growth promotion which comprises, as an essential component, a compound of the formula I: wherein R is or H, or a salt thereof.
  • the invention permits a method for growth promotion in animals, which comprises administering an effective amount of a compound of the above formula I or a salt thereof in admixture with conventional carriers and/or ingredients for an animal feed.
  • the invention provides the use of a compound of formula I of the invention, or a salt thereof, in the manufacture of an animal growth-promoting preparation.
  • the agent for use in the invention may be mode by a method which comprises formulating for veterinary use a compound of formula I of the invention, or a salt thereof, optionally in the form of a premix for mixing with animal feed or in the form of an animal feed ration.
  • the invention permits the production of an animal exhibiting enhanced growth after being subjected to treatment using the growth promotion agent described herein.
  • glycopeptide antibiotics including vancomycin, and their derivatives.
  • the administration of such antibiotics to animals may promote growth of the animals.
  • EP-A-231 111 discloses glycopeptides as antibiotics but makes no invention of any growth promotion activity.
  • a compound of the above formula I wherein R is is known and disclosed as PA-42867-A in Japanese Patent Publication No. 174099/1987, and a compound of the above formula I wherein R is or H is also known and disclosed as des-(4-epi-vancosaminyl)PA-42867-A or des-(4-epi-vancosaminyl-0-glucosyl)PA-42867-A in Japanese Patent Publication No. 1088865/1989.
  • vancomycin antibiotics are also known to have a growth-promoting action on animals. However, nothing is known about the growth-promoting action of the compounds used according to the present invention.
  • the inventors have found that the above-mentioned compounds have a strong antibacterial activity on strains belonging to the genus Clostridium , said activity being helpful for evaluating the growth-promoting action of the compounds, and have also found that the application of the said compounds to animals leads to a remarkable increase in body weight.
  • glycopeptide compounds per se used according to the present invention may be applied directly to animals by, for example, oral administration, they are often applied in the form of a premix which is prepared by mixing the glycopeptide(s) with conventional carriers such as defatted rice bran, defatted soybean flour, bran, kaolin, talk, calcium carbonate, lactose, water, etc.
  • conventional carriers such as defatted rice bran, defatted soybean flour, bran, kaolin, talk, calcium carbonate, lactose, water, etc.
  • such a premix or the glycopeptide compounds per se may be applied to animals after mixing with conventional animal feeds.
  • a preferred embodiment of the agent used according to the present invention is an animal feed ration for growth promotion, and therefore, the subsequent explanation is prefentially directed to animal feeds containing the above-mentioned glycopeptide compounds.
  • glycopeptide compounds used here are not necessarily required to be pure materials; for instance, a culture medium in which a glycopeptide-producing microorganism has been cultured can be employed as a whole after partial purification.
  • Veterinarily acceptable salts of the glycopeptides may also be used, and include, for example, salts with alkali metals such as potassium and sodium; salts with alkaline-earth metals such as magnesium and aluminium; salts with inorganic acids such as hydrochloric acid, sulfuric acid and nitric acid; and salts with organic acids such as acetic acid and fumaric acid.
  • any material usually used as a feed component for animals may be employed.
  • examples of such material are corn, bran, rice, wheat or barley, cotton seed meal, milo, soybean meal, fish meal, defatted rice bran, oil and fat, alfalfa, calcium carbonate, calcium phosphate, sodium chloride, choline chloride, vitamins such as vitamin A, vitamin D, vitamin E, vitamin B1, vitamine B2, vitamin B6, vitamin B12, calcium pantothenate, nicotinamide and folic acid, inorganic salts such as magnesium sulfate, iron sulfate, copper sulfate, zinc sulfate, potassium iodide and cobalt sulfate. All of part of these materials may be mixed with one or more of the glycopeptides. Besides, other antibiotics, bactericides, anti-coccidium agents, vermifuges and the like may also be added.
  • the growth-promoting agent used according to the invention may be used for various animals.
  • animals are poultry and domestic animals, including chicken, turkey, duck, quail, cow, horse, pig, sheep, goat, mink, rabbits and the like. These animals may be raised in a conventional manner.
  • the daily dosage of one or more of the glycopeptides used according to the present invention ranges from 0.01 to 3.0 mg per kg of the body weight of an animal, irrespective of whether glycopeptide(s) per se is/are used, or a microorganism culture containing the glycopeptides is used, or an extracted crude material containing the glycopeptides is used.
  • a dosage of from 0.3 to 3.0 mg/kg/day is preferred for poultry, while a dosage of from 0.01 to 1.0 mg/kg/day is preferred for cattle and swine.
  • the content of the glycopeptide(s) used according to the invention in an animal feed will generally range from 0.5 ppm to 100 ppm.
  • the growth-promoting agent used according to the present invention not only promotes the growth of animals, but also improves feed utilization efficiency.
  • the agent is also effective for the treatment of bacterial diseases. Moreover, its toxicity in animals is low, and it does not remain in animal bodies. There are advantageous characteristics of the agent used according to the invention. LD50 values of the compounds used according to the present invention when intravenously injected in male mice are shown below:
  • a seed slant culture of Nocardia sp. PA-42867 (FERM BP-1230) is inoculated into an Erlenmeyer flask (2 L) charged with 800 ml of the broth comprising 0.5% soluble starch, 0.5% glucose, 0.5% polypeptone, 0.5% meat ext., 0.25% yeast ext., 0.25% sodium chloride, and deionized water (pH 7.0 before sterilization), and fermented with shaking at 180 r.p.m. at 28°C for 48 hours.
  • This fermented broth (800 ml) is transplanted into a jar-fermenter (30 L) charged with 20 L of the same broth as noted above, and fermented at 28°C for 24 hours with stirring at 200 r.p.m. (aeration rate 20 L/min., and internal pressure 0.5 Kg/cm2G).
  • 10 L of the resulting broth is transplanted into a fermentation tank (250 L) changed with 140 L of the broth comprising 2.4% tomato paste, 2.4% dextrin, 1.2% dried yeast (Beast, Iwaki Seiyaku Co., Ltd.), 0.0006% cobalt chloride hexahydrate, 0.08% defoamer P-2000 (Dai Nippon Ink & Chemicals Inc.) and tap water (pH 7.0 before sterilization), and fermented at 28°C for 64 hours with stirring at 325 r.p.m. (aeration rate 150 L/min., and internal pressure 5 p.s.i.).
  • the fermented broth prepared in the above step which is adjusted to pH 10.5 with 10% sodium hydroxide, is centrifuged to give 145 L of supernatant. Adjusted to pH 4.0, the supernatant is applied to a column charged with 13 L of Dowex 50 x 2 (Na+ type) (Dow Chemical Co.), washed with 70 L of water, and eluted with 40 L of 30% acetone water containing 1% triethylamine.
  • the fractions showing activity by the pulp disc dispersion method employing Bacillus subtilis are collected (22 L), adjusted to pH 5.0, and then condensed by evaporating acetone under reduced pressure.
  • the above crude powder (12 g) is dissolved in 150 ml of 0.01 N hydrochloric acid, and applied to a column of 100 ml of MCI GEL CHP-20P (Mitsubishi Chemical Industries Co.). The column is eluted with 0.01 N hydrochloric acid as tracing out the content of PA-42867 with HPLC. The fractions containing PA-42867-A and -B are adjusted to pH 7.0 and chromatographed again with CHP-20P column.
  • the fractions containing PA-42867-A and -B are applied to the column, washed well with 15% methanol water, and eluted with 15% methanol-0.005 N hydrochloric acid, to give a fraction containing PA-42867-A and a fraction containing PA-42867-B.
  • the fraction containing PA-42867-A is adjusted to pH 7.0 and condensed.
  • the resultant is applied to a column of 10 ml of CHP-20P and then eluted with dilute hydrochloric acid (pH 5.0) to give the fraction containing PA-42867-A, which is condensed and lyophilized to give 571 mg of the residue (70% purity).
  • dilute hydrochloric acid pH 5.0
  • the solution is applied to a column of 10 ml of CHP-20P and eluted with water to give the fraction of PA-42867-A, which is adjusted to pH 7.0 and condensed.
  • the fraction containing PA-42867-B as noted above is adjusted to pH 7.0, condensed and lyophilized to give 683 mg of the residue.
  • the residue (683 mg) of PA-42867-B disslved in water is adjusted to pH 4.0 by adding dilute hydrochloric acid, applied to a column of 5 ml of CHP-20P for the purpose of decoloration and eluted with dilute hydrochloric acid (pH 4.0) to give the fraction of PA-42867-B, which is adjusted to pH 7.0 and condensed.
  • the solution is applied to MCI GEL CHP-20P (200 to 400 mesh, 100 ml), and eluted with successive, water (600 ml), 0.01 N hydrochloric acid (450 ml), water (450 ml), 25% methanol water (450 ml), 50% methanol water (400 ml), methanol (400 ml), and 50% methanol - 0.005 N hydrochloric acid (400 ml).
  • fraction check with HPLC (Nucleosil 300-7C18, 4.6 ⁇ x 250 mm, 10% acetonitrile-0.05 M PBS (pH 3.5), flow rate 1 ml/min., 220 nm UV detection), fraction A (0.01 N hydrochloric acid- and water-elution portions) and fraction B (50% methanol-, methanol-, and 50% methanol-0.005 N hydrochloric acid-elution portions) are obtained.
  • HPLC Nucleosil 300-7C18, 4.6 ⁇ x 250 mm, 10% acetonitrile-0.05 M PBS (pH 3.5), flow rate 1 ml/min., 220 nm UV detection
  • fraction A (0.01 N hydrochloric acid- and water-elution portions
  • fraction B 50% methanol-, methanol-, and 50% methanol-0.005 N hydrochloric acid-elution portions
  • Fraction B is concentrated, adjusted to pH 3.5, applied to MCI GEL CHP-20P (200 to 400 mesh, 10 ml), and eluted with successive, 300 ml of water (adjusted to pH 4.0 by hydrochloric acid water, about 10 ⁇ 4 N hydrochloric acid), 100 ml of 15% methanol water (pH 4.0), 100 ml of 30% methanol water (pH 4.0), 100 ml of 50% methanol water (pH 4.0), 50 ml of methanol, and 50 ml of 50% methanol-0.005 N hydrochloric acid to obtain fraction C (water (pH 4.0)-elution portion) and fraction D (50% methanol-water (pH 4.0)-elution portion).
  • Fractions A and C are put together, concentrated, adjusted to pH 7.0, and desalted by using MCI GEL CHP-20P (200 to 400 mesh, 10 ml); eluted with successive, water (100 ml), 25% methanol water (100 ml), 50% methanol water (100 ml), methanol (100 ml), and 50% methanol-0.005 N hydrochloric acid (50 ml) to obtain fraction E (not-desalted portion) and fraction F (desalted portion). Fraction E (not-desalted portion) is desalted again in the same conditions to obtain fraction G (desalted portion).
  • fraction I 0.01 N hydrochloric acid- and water-elution portions
  • fraction II 50% methanol-, methanol-, and 50% methanol-0.005 N hydrochloric acid-elution portions
  • Fraction II is concentrated, adjusted to pH 3.5, applied to MCI GEL CHP-20P (200 to 400 mesh, 10 ml), and eluted with successive, 50 ml of water (pH 4.0), 15% methanol-water (pH 4.0), 30% methanol-water (pH 4.0), 50% methanol-water (pH 4.0), 50 ml of mehtanol, and 50 ml of 50% mehtanol-0.005 N hydrochloric acid, to obtain fraction III [water (pH 4.0)-elution portion] and fraction IV [50% methanol-water (pH 4.0)-, and 50% methanol-0.005 N hydrochloric acid-elution portions].
  • Nocardia sp. PA-42867 which produces PA-42867-A was deposited as Nocardia orientalis PA-42867 with the Fermentation Research Institute, Agency of the Industrial Science & Technology, Higashi 1-1-3, Tsukuba City, Ibaragi Prefecture, on January 8, 1986 under accession No. Bikoken Kinki 8601 (FERM P-8601), and changed to a deposition according to the Budapest Treaty, on December 4, 1986 (FERM BP-1230).
  • PA-42867-A (Compound 1), des-(4-epi-vancosaminyl) PA-42867-A (Compound 2), and des-(4-epi-vancosaminyl-O-glucosyl)PA-42867-A (Compound 3) were subjected to anti-microorganism tests using Clostridium perfringens , and their growth promoting actions were measured on chicks.
  • PA-42867-A Growth promoting effect of PA-42867-A on chicks (8 days of age, Abaeker species) was determined using a known antibiotic, Thiopeptin, as a control.
  • PA-42867-A and Thiopeptin were added to an antibiotic-free feed mash (crude protein content (CP): 18%) at a concentration of 20 ppm, and the chicks were raised for 10 days with the resulting feed according to the battery method.
  • the above feeding was conducted after dividing the chicks in each of these groups into sub-groups of 6 - 7 chicks and putting each sub-group in a cage (435 x 600 x 410 mm).
  • the feeding was conducted for 10 days (until 18 days of age) at an environmental temperature of 26 ⁇ 2°C.
  • the effectiveness of the drug was evaluated based on the body weight gain and the feed efficiency observed during the 10 days period of the experiment. The results are as shown in Table 2.
  • the group which received PA-42867-A showed a significantly high body weight gain (p ⁇ 0.01).
  • the PA-42867-A group and Thiopeptin group showed better results in feed efficiency as compared with the group raised with the antibiotic-free feed.
  • the newly hatched chicks were fed until eight days of age with a feed mash (crude protein content (CP):23%) without addition of any antibiotic by means of the flat feeding. Then, the chicks were divided into four groups each containing 24 chicks (males and females, 12 each). Each group was placed in four cages after dividing into four unisexual sub-groups, each consisting of 6 - 7 chicks, and raised for 13 days with an animal feed of CP 18% with or without antibiotics.
  • CP crude protein content
  • each of four groups received 20 ppm of des-(4-epi-vancosaminyl)PA-42867-A, 20 ppm of des-(4-epi-vancosaminyl-O-glucosyl)PA-42867-A, 20 ppm of Thiopeptin, and no antibiotic, respectively.
  • the animal feeds used according to the present invention which promote animal growth, can be prepared in conventional ways and are illustrated by the following Examples.
  • the above ingredients are mixed well to give an animal feed for poultry or swine.
  • Des-(4-epi-vancosaminyl)PA-42867-A or des-(4-epi-vancosaminyl-O-glucosyl)PA-42867-A is mixed with other ingredients in the same manner as in Examples 1, 2 or 3 mentioned above, to give an animal feed for poultry or swine.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Polymers & Plastics (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Food Science & Technology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Claims (5)

  1. Verfahren zur Herstellung einer Formulierung zur Förderung des Tierwachstums, gegebenenfalls in Form eines Premix zum Vermischen mit Tierfutter oder in Form einer Tierfutterration, wobei das Verfahren dadurch gekennzeichnet ist, daß es die Verwendung als wesentlichen Bestandteil eines oder mehrerer Glycopeptide der Formel I umfaßt:
    Figure imgb0019
     in der R
    Figure imgb0020
     oder ein Wasserstoffatom bedeutet, oder eines Salzes (Salzen) davon, in einer solchen Weise, daß das (die) Glycopeptid(e) der Formel (I) oder ein Salz(e) davon unter hinreichenden Bedingungen mit einem geeigneten Träger zu dem Premix vermischt wird (werden); oder das (die) Glycopeptid(e) oder ein Salz(e) davon zur Herstellung der Tierfutterration unter hinreichenden Bedingungen mit ein oder mehreren Produkten vermischt wird (werden), die normalerweise als Tierfutterbestandteile verwendet werden; wobei gegebenenfalls Antibiotika, Bakterizide, anticoccidiale Mittel, Helminthagoga und dgl. ebenfalls zugegeben werden können.
  2. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß das (die) Glycopeptid(e) der Formel (I) oder ein Salz(e) davon in Form einer dasselbe (dieselben) enthaltenden Mikroorganismuskultur, oder in Form eines Rohextrakts einer solchen Kultur bei dem Verfahren verwendet wird (werden).
  3. Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß das (die) Salz(e) des (der) Glycopeptids(e) der Formel (I) ausgewählt wird (werden) unter anderem aus der Gruppe von Salzen mit Alkalimetallen, wie Natrium oder Kalium; Salzen mit Erdalkalimetallen, wie Magnesium und Aluminium; Salzen mit anorganischen Säuren, wie Salzsäure, Schwefelsäure und Salpetersäure, und Salzen mit organischen Säuren, wie Essigsäure und Fumarsäure.
EP89300764A 1988-01-26 1989-01-26 Verwendung eines Mittels zum Fördern des Tierwachstums Expired - Lifetime EP0327259B1 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT89300764T ATE88614T1 (de) 1988-01-26 1989-01-26 Verwendung eines mittels zum foerdern des tierwachstums.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP63015341A JPH01190633A (ja) 1988-01-26 1988-01-26 動物用成長促進剤
JP15341/88 1988-01-26

Publications (3)

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EP0327259A2 EP0327259A2 (de) 1989-08-09
EP0327259A3 EP0327259A3 (en) 1990-11-07
EP0327259B1 true EP0327259B1 (de) 1993-04-28

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US (1) US4906612A (de)
EP (1) EP0327259B1 (de)
JP (1) JPH01190633A (de)
KR (1) KR950013454B1 (de)
AT (1) ATE88614T1 (de)
AU (1) AU611251B2 (de)
CA (1) CA1328188C (de)
DE (1) DE68906172T2 (de)
ES (1) ES2040993T3 (de)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AUPQ137699A0 (en) * 1999-07-02 1999-07-22 University Of New England, The Control of acidosis
KR102485194B1 (ko) * 2020-12-15 2023-01-06 전남대학교산학협력단 LFRFamide 펩타이드를 유효성분으로 함유하는 복족류의 산란 유도용 조성물

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4637981A (en) * 1980-12-18 1987-01-20 Eli Lilly And Company Antibiotic A-4696 factor G
US4659660A (en) * 1982-07-30 1987-04-21 Eli Lilly And Company A47934 antibiotic and process for production thereof
US4537879A (en) * 1982-07-30 1985-08-27 Eli Lilly And Company A47934 Antibiotic and process for production thereof
JPS6030690A (ja) * 1983-07-15 1985-02-16 Sankyo Co Ltd 抗生物質クロロポリスポリン
US4558036A (en) * 1984-02-17 1985-12-10 Eli Lilly And Company Actaplanin antibiotics
US4694069A (en) * 1985-09-30 1987-09-15 Smithkline Beckman Corporation Kibdelosporangium aridum SK&F-AAD-609
US4946941A (en) * 1986-01-24 1990-08-07 Shionogi & Co., Ltd. Novel glycopeptide antibiotics
JPS62174099A (ja) * 1986-01-24 1987-07-30 Shionogi & Co Ltd 新規グリコペプチド系抗生物質ｐａ−４２８６７−ａおよびｐａ−４２８６７−ｂとその製造方法
US4742045A (en) * 1986-07-30 1988-05-03 Smithkline Beckman Corporation Glycopeptide antibiotics
IE873523L (en) * 1986-12-30 1988-06-30 Memorex Corp Glycosylated glycopeptides
US5071749A (en) * 1987-04-16 1991-12-10 Shionogi & Co., Ltd. Glycopetide antibiotic pa-45052-b

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EP0327259A2 (de) 1989-08-09
DE68906172T2 (de) 1993-11-11
KR890011901A (ko) 1989-08-23
ATE88614T1 (de) 1993-05-15
JPH0462300B2 (de) 1992-10-05
KR950013454B1 (ko) 1995-11-08
AU2874989A (en) 1989-07-27
CA1328188C (en) 1994-04-05
DE68906172D1 (de) 1993-06-03
ES2040993T3 (es) 1993-11-01
AU611251B2 (en) 1991-06-06
US4906612A (en) 1990-03-06
JPH01190633A (ja) 1989-07-31
EP0327259A3 (en) 1990-11-07

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